Management of acute, life-threatening neurologic illnesses, such as severe traumatic brain injury, is facilitated by accurate and continuous monitoring of cerebral oxygenation. However, current monitoring systems are invasive, requiring either cannulation of the internal jugular venous bulb or insertion of a probe directly into the brain. Nearinfrared spectroscopy, a noninvasive method of monitoring cerebral blood oxygenation, is promising, but has yet to be satisfactorily calibrated to provide quantitative measurement in adults. At present there is no system for accurate, noninvasive, and continuous monitoring of cerebral blood oxygenation. We proposed and performed in vitro and in vivo testing of a novel optoacoustic technique that accurately and continuously measures blood oxygenation directly from the superior sagittal sinus, a structure that can easily be localized due to the high resolution of the optoacoustic technique. The optoacoustic technique is based on generation of ultrasonic (optoacoustic) waves by laser pulses and detection of these waves by a sensitive acoustic transducer. Optoacoustic monitoring of blood oxygenation utilizes well-established differences in the optical absorption coefficients of oxy- and deoxyhemoglobin in the nearinfrared spectral range. During our current NIH R21 project supported by an NINDS grant under the Program Announcement PA-98-050 (directed at the development of innovative technologies including photoacoustic brain monitoring), we designed, built, and tested a noninvasive optoacoustic system for accurate monitoring of cerebral blood oxygenation. Our in vitro and in vivo (in sheep) studies demonstrated that: (1) the parameters of the optoacoustic waves are linearly dependent on blood oxygenation; (2) the use of specially designed transducers and optoacoustic probes allows sensitive detection despite optical and acoustic attenuation by thick bone; and (3) this technique can measure blood oxygenation with high accuracy. In this grant application, we propose to further develop this technique under this program announcement. The specific aims of the project are: (1) to modify the optoacoustic system to provide multiwavelength measurements and perform evaluation of the system in cadavers; (2) to evaluate it in vivo in volunteers; and (3) to evaluate the system performance in patients with traumatic brain injury. By the end of the project the system will be developed sufficiently to permit multi-center clinical trials.